Hepatitis C virus (HCV) is a main human pathogen and there are about 200 million cases infected with HCV worldwide. Chronic HCV infection will develop advanced progressive liver diseases, including cirrhosis and hepatocellular carcinoma. Therefore, chronic HCV infection is one of the major causes of death worldwide in patients who suffer from liver diseases. According to data released by the Health Planning Commission, the reported cases of hepatitis C virus (HCV) infection in China has increased year by year in the past 10 years, and the general situation tends to be negative.
HCV is a positive-strand RNA virus, and its genome consists of approximately 9,600 nucleotides, including non-coding regions at both ends, i.e., an internal ribosome entry site (IRES) and an open reading frame (ORF). HCV genome comprises 10 genes that are expressed to produce a total of 10 structural proteins (a core protein, envelope proteins E1 and E2, an ion channel protein P7) and non-structural proteins (NS2, NS3, NS4A, NS4B, NS5A and NS5B). NS5A is an HCV non-structural protein 5A whose function is not fully understood. Currently, it is believed that NS5A is associated with formation of viral replication complex and virus-host interaction. Therefore, NS5A is essential for the life cycle of virus and virus replication is highly sensitive to its inhibitions (inhibitors of NS5A has a strong antiviral activity in vitro).
Currently, combination therapy of α-interferon and a broad-spectrum antiviral drug ribavirin is used as a standard therapy for treating hepatitis C. For a monotherapy, the PEGylated α-interferon is superior to the unmodified α-interferon. The latest clinical results show that the therapeutic effect is significantly improved using combination of PEGylated α-interferon and ribavirin as compared to the combination of alpha-interferon and ribavirin. However, it still does not work for some patients with chronic HCV infection leading to side effects to many patients, and thus is not suitable for a long-term treatment.
Therefore, there is a need to develop a novel and effective drug for treating the chronic HCV infection.